The efficacy and underlying mechanism of phosphodiesterase- 5 inhibitors in preventing cognitive impairment and Alzheimer pathology: A systematic review of animal studies

El-Bakly, Wesam M.; Wagdy, Omar; Sobhy, Ahmed; elenain, Omar abo; Riad, Mohamed S.; Sayed, Manal M.; Tarkhan, Sherif; Yassen, Mahmoud; Mahmoud, Abdelrahman; Bassiony, Mohamed; Nabil, Nesreen

doi:10.1016/j.bbr.2019.112004

Cited by 10 publications

(4 citation statements)

References 55 publications

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“…Nevertheless, correlation analysis of the association between Aβ pathology and cognitive function showed that Aβ-42 was not significantly related to cognitive changes ( El-Bakly et al, 2019 ). Instead of Aβ precipitation, glial cells directly affect behavioral function.…”

Section: Discussionmentioning

confidence: 99%

Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies

et al. 2023

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Objective: Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer’s disease (AD).Methods: A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition. The methodological quality of each selected pre-clinical study was evaluated using the SYRCLE risk of bias tool. A random-effects model was applied to analyze the data and calculate the effect size, while I2 and p-values were used to assess heterogeneity.Results: The analysis included 26 original articles describing (1050 rodents) with AD-like symptoms. Rodents treated with cannabinoid agonists showed significant reductions in escape latency (standard mean difference [SMD] = −1.26; 95% confidence interval [CI]: −1.77 to −0.76, p < 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76, p < 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = −0.91; 95% CI: −1.55 to −0.27, p = 0.006) was observed in the endocannabinoid-treated group compared to the control group. Trends were observed toward neuroprotection, as represented by decreased levels of glial cell markers including glial fibrillary acid protein (SMD = −1.47; 95% CI: −2.56 to −0.38, p = 0.008) and Iba1 (SMD = −1.67; 95% CI: −2.56 to −0.79, p = 0.0002). Studies on the wild-type mice demonstrated significantly decreased levels of pro-inflammatory markers TNF-α, IL-1, and IL-6 (SMD = −2.28; 95% CI: −3.15 to −1.41, p = 0.00001). Despite the non-significant decrease in pro-inflammatory marker levels in transgenic mice (SMD = −0.47; 95% CI: −1.03 to 0.08, p = 0.09), the result favored the endocannabinoid-treated group over the control group.Conclusion: The revised data suggested that endocannabinoid stimulation promotes cognitive function via modulation of glial cells by decreasing pro-inflammatory markers in AD-like rodent models. Thus, cannabinoid agents may be required to modulate the downstream chain of effect to enhance cognitive stability against concurrent neuroinflammation in AD. Population-based studies and well-designed clinical trials are required to characterize the acceptability and real-world effectiveness of cannabinoid agents.Systematic Review Registration: [https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770].

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Section: Discussionmentioning

confidence: 99%

Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies

et al. 2023

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“… 29 , 30 The checklist was originally developed to assess preclinical models of ischaemic stroke, 29 , 30 but has been used for models of other neurological conditions including TBI, cardiac arrest, Alzheimer's disease, and Parkinson's disease. 63 , 64 , 65 , 66 , 67 There was one moderate-quality study in the argon group, that had the highest effect size of that group. There were seven moderate quality studies in the xenon group distributed equally on both sides of the summary effect estimate.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by the noble gases argon and xenon as treatments for acquired brain injury: a preclinical systematic review and meta-analysis

Liang

Ahmad

Dickinson

2022

British Journal of Anaesthesia

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“…ER stress modulators, autophagy-enhancing drugs, gene therapy, and anti-amyloid immunotherapy are also being examined as therapeutic approaches in the treatment of AD [146,[220][221][222]. In recent years, sildenafil, a known inducer of autophagy, has been associated with the alleviation of cognitive impairment in pre-clinical models and decreased incidence of AD in human studies and, thus, has been proposed as a candidate drug that could be repurposed for AD treatment [223,224]. The potential of sildenafil use for the treatment of AD has not yet been verified as evidence from a recent study does not support previous claims [225].…”

Section: Treatmentmentioning

confidence: 99%

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

Medegan Fagla,

Buhimschi

2024

Molecules

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Protein misfolding disorders are a group of diseases characterized by supra-physiologic accumulation and aggregation of pathogenic proteoforms resulting from improper protein folding and/or insufficiency in clearance mechanisms. Although these processes have been historically linked to neurodegenerative disorders, such as Alzheimer’s disease, evidence linking protein misfolding to other pathologies continues to emerge. Indeed, the deposition of toxic protein aggregates in the form of oligomers or large amyloid fibrils has been linked to type 2 diabetes, various types of cancer, and, in more recent years, to preeclampsia, a life-threatening pregnancy-specific disorder. While extensive physiological mechanisms are in place to maintain proteostasis, processes, such as aging, genetic factors, or environmental stress in the form of hypoxia, nutrient deprivation or xenobiotic exposures can induce failure in these systems. As such, pregnancy, a natural physical state that already places the maternal body under significant physiological stress, creates an environment with a lower threshold for aberrant aggregation. In this review, we set out to discuss current evidence of protein misfolding in pregnancy and potential mechanisms supporting a key role for this process in preeclampsia pathogenesis. Improving our understanding of this emerging pathophysiological process in preeclampsia can lead to vital discoveries that can be harnessed to create better diagnoses and treatment modalities for the disorder.

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The efficacy and underlying mechanism of phosphodiesterase- 5 inhibitors in preventing cognitive impairment and Alzheimer pathology: A systematic review of animal studies

Cited by 10 publications

References 55 publications

Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies

Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies

Neuroprotection by the noble gases argon and xenon as treatments for acquired brain injury: a preclinical systematic review and meta-analysis

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

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